title: Ghilantens: anticoagulant-antimetastatic proteins from the South American leech, Haementeria ghilianii.
abstract: Five proteins with anticoagulant and antimetastatic activities were isolated from the salivary glands of the Amazon leech, Haementeria ghilianil. These proteins, designated ghilantens, were co-purified on DEAE-cellulose and heparin-agarose, and were purified by microbore C-18 reverse-phase HPLC. Each variant had a similar molecular weight (18,000), amino acid composition, and a blocked amino terminus. Ghilantens caused a dose-dependent prolongation of the prothrombin time of normal human plasma and blocked the factor Xa-mediated hydrolysis of methoxycarbonyl-D-cyclohexylglycyl-glycl-arginine-p-nitro anillide acetate. Ghilantens were quantitatively absorbed to bovine factor Xa-AffiGel-15 and were eluted with 0.1 mol/L benzamidine, an active-site reversible inhibitor of factor Xa. These findings show that ghilantens can form a reversible association with the enzyme. When administered intravenously to mice by tall vein injection, ghilantens potently suppressed lung metastases of B16-F10 melanoma cells. These findings suggest that ghilantens may have therapeutic value in the treatment of metastatic disease.
authors.affiliation: Merell Dow Research Institute, Cincinnati, OH 45215-6300.
authors.forename: R G
authors.initials: RG
authors.lastname: Brankamp
authors.forename: D T
authors.initials: DT
authors.lastname: Blankenship
authors.forename: P S
authors.initials: PS
authors.lastname: Sunkara
authors.forename: A D
authors.initials: AD
authors.lastname: Cardin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000032:analysis / Q000302:isolation & purification*; D000970:Antineoplastic Agents / Q000032:analysis / Q000302:isolation & purification*; D007865:Leeches / Q000032:analysis*; D008969:Molecular Sequence Data; D012469:Salivary Glands / Q000032:analysis; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000302:isolation & purification*
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D012471:Salivary Proteins and Peptides